A variety of drugs, toxins, carcinogens and other xenobiotics, including common dietary constituents, food additives or contaminants, undergo biotransformation in the intestinal mucosa. In general, such biotransformation results in inactivation of the parent compound, although potential metabolic activation to more potent pharmacological, carcinogenic, or toxic metabolites also occurs. In the intestinal mucosa, as in the liver, most of these inactivation reactions are catalyzed by microsomal cytochrome P-450 exists along the duodenal mucosal villus with the highest concentration occurring in the most mature tip cells. Cytochrome P-450 is inducible by its substrates, and such induction requires enhanced synthesis of heme and of apocytochrome P-450 in the liver. The localization, coordination, and regulation of these two synthetic processes in the intestinal mucosa have not yet been determined. The proposed studies are designed to investigate the particular cellular localization and the mechanism of synthesis of intestinal cytochrome P-450 and of its constitutive moieties, and to characterize the effect of exogenous (drugs, dietary components, iron-deficient diet, etc.) and endogenous (hormones) regulators on these processes. The findings are expected to clarify the role of the intestine in the metabolism of drugs, carcinogens, and other toxins and to define the regulation of this process.